Department of Biological Sciences

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Author: search.filters.author.Dubey, Uma S.Has files: No

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    Proteomics analysis in urinary bladder cancer patients identifies urinary SOD2 as a predictive marker of recurrence
    (2021-12) Dubey, Uma S.
    Early non-invasive detection of tumor is an urgent clinical need for managing urothelial bladder cancer. Cystoscopy and cytology are the current standards for diagnosis of recurrence, but are limited by low sensitivity. Quantitative proteomics tool was employed to identify important deregulated molecules in bladder cancer tissues and validated using Western blot and immunohistochemistry analysis. A set of 1137 proteins were identified in four paired bladder cancer patients. Among these, 64 proteins were deregulated in all cases among which 9 were commonly up-regulated. The Ingenuity Pathway Analysis (IPA) generated top 11 Networks in which three commonly upregulated (SERPING1, SOD2 and HSPB6) proteins were involved and selected for further validation. Tissue expression of SOD2, SERPING1 and HSPB6 monitored in an independent sample set (n=18) by immuno-histochemical analysis showed similar profile. Western blot analysis of these proteins in urine of bladder cancer (n=26) and healthy subjects (n=10) showed a specificity and sensitivity of >80% for SOD2 and so was selected for further validation in a separate set (n=150) by ELISA. Significant elevation in urinary SOD2 level was found in urothelial bladder cancer patients compared to healthy controls and in recurrent cases compared to primary (p-value<0.001). Kaplan Meier survival analysis showed urinary SOD2 concentration >2,100 pg/ml was significantly associated with poorer survival.Cumulative survival of patient with low SOD2 concentration was 34.4% compared to 18.9% in patient with high SOD2 at 24 months (p=0.025). The study identifies SOD2 as a non-invasive biomarker which may help to extend the period between cystoscopies during follow-up.
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    Calcium chloride linked camel milk derived casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells
    (Tech Science Press, 2021-09) Dubey, Uma S.
    Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.
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    Medicinal potential of Camel milk lactoferrin
    (Intecopen, 2022) Dubey, Uma S.
    Camel milk is a rich source of protein with well-recognized medicinal properties to treat various diseases. The objective of this work is to understand the role of camel milk lactoferrin in immunomodulation and in disease treatment. It has been found that camel milk lactoferrin is a very suitable nutraceutical agent by virtue of its bioac- tivity, immuno-compatibility, and safety. It can be used for the treatment of infec- tious, metabolic, and neurodegenerative diseases, besides cancer. It is a cost-effective biomolecule that also has high relative abundance and bioavailability.
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    Studies on cytotoxic activity of Camel milk whey protein as a nutraceutical against HeLa cells
    (Camel Publishing House, 2023) Dubey, Uma S.
    Camel milk is an adapted dietary supplement with multiple antimicrobial and immuno-stimulatory properties. Diabetes, infant diarrhoea, hepatitis, allergy, lactose intolerance, and alcohol- induced liver damage have been treated with it (Galil et al, 2016). Numerous immunologically essential molecules, such as lysozymes, lactoferrin, lactoperoxidase, serum albumin, acidic whey protein, peptidoglycan recognition protein, and small peptides, contribute to its health benefits (Dubey et al, 2016). Recently, the anti-microbial and antioxidant properties of camel milk and its role as an anti-cancer and anti-hepatitis agent has been demonstrated (Khan et al, 2021). Camel milk also has the normal isotypes of antibodies shared with other mammalian species. Actually not only camel’s milk but even its urine is among such natural products enriched with molecules that are safe to humans and endowed with profound anti-cancer properties (Alebie et al, 2017). Aryl hydrocarbon receptor (AhR) is an endogenous transcription factor with known preventative and therapeutic benefits for patients with cancer associated with organs like the liver, breast, prostate, etc. (Xie et al, 2012; Richmond et al, 2014). Aberrant AhR expression is involved in carcinogenesis (Korzeniewski et al, 2010).
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    Aberrant expression of col14a1, celrs3, and cthrc1 in breast cancer сells
    (Experimental oncology, 2023) Dubey, Uma S.
    Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling. Aim: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC. Materials and Methods: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients. Results: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes. Conclusion: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.
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    Evaluation of the cytotoxic activity of sorafenib-loaded camel milk casein nanoparticles against hepatocarcinoma cells
    (Wiley, 2024-03) Dubey, Uma S.
    Sorafenib, a multikinase inhibitor is used to treat hepatocellular and renal carcinoma. However, a low solubility impedes its bioavailability and thus, effectiveness. This study aims to enhance its effectiveness by using novel camel milk casein nanoparticles as a delivery system. This study evaluates the cytotoxicity of sorafenib encapsulated in camel milk casein nanoparticles against human hepatocarcinoma cells (HepG2 cells) in vitro. Optimal drug loaded nanoparticles were stable for 1 month, had encapsulation efficiency of 96%, exhibited a particle size of 230 nm, zeta potential of −14.4 and poly disparity index of 0.261. Treatment with it led to cell morphology and DNA fragmentation as a characteristic of apoptosis. Flow cytometry showed G1 phase arrest of cell cycle and 26% increased apoptotic cells population upon treatment as compared to control. Sorafenib-loaded casein nanoparticles showed 6-fold increased ROS production in HepG2 cells as compared to 4-fold increase shown by the free drug. Gene and protein expression studies done by qPCR and western blotting depicted upregulation of tumor suppressor gene p53, pro-apoptotic Bax, and caspase-3 along with downregulated anti-apoptotic Bcl-2 gene and protein expression which further emphasized death by apoptosis. It is concluded regarding the feasibility of these casein nanoparticles as a delivery system with enhanced therapeutic outcomes against hepatocellular carcinoma cells.
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    Modeling the effect of vaccinations, hospital beds, and treatments on the dynamics of infectious disease with delayed optimal control and sensitivity analysis
    (Springer, 2024-08) Dubey, Uma S.; Dubey, Balram
    Immunization plays a vital role in eradicating infectious diseases, typically requiring multiple doses at specific time intervals. This study focuses on developing and analyzing an infectious disease model governed by a six-dimensional system of ordinary differential equations, considering the impact of first and second vaccination doses along with hospital beds and treatment. The model’s qualitative behavior is analyzed, including conditions for positive solutions, the invariant region of the solution, equilibrium points, and their stability. When the basic reproduction number () is less than one (), the disease will be eradicated; conversely, an epidemic occurs when . Moreover, the transcritical bifurcation of the system is examined using the center manifold theory. Interestingly, backward bifurcation is discovered, and it indicates that the disease is not entirely eradicated even when . We have investigated different bifurcations like saddle-node, transcritical, and Hopf bifurcations of codimension 1, as well as Generalized-Hopf (GH), Cusp (CP), and Bogdanov–Takens (BT) bifurcations of codimension 2. Additionally, a delayed epidemiological model is explored, assuming a lag in vaccination among the susceptible population. A Hopf-bifurcation is observed near the endemic equilibrium point, linked to critical parameter values during the latent period. Moreover, the model is calibrated using the least-squares technique, incorporating coronavirus-infected case data and vaccination information from India and Italy’s mass vaccination program between March 1, 2021, and May 30, 2021. Global sensitivity analysis, utilizing the Partial Rank Correlation Coefficient (PRCC), identifies crucial parameters affecting threshold quantities after fitting the model. The study highlights the significance of critical parameters such as the effective transmission rate, rates of first and second-dose vaccinations, and recovery rate due to double-dose vaccination. Further, delayed optimal control measures are determined using Pontryagin’s maximal principle to mitigate infection, prevention, and treatment burdens. Numerical simulations are conducted to understand the effect of these delayed control measures on disease progression and demonstrate the insights obtained through analytical investigations. The study indicates that implementing all control strategies effectively reduces the disease burden among the population. Accurate estimation of vaccine efficacy is crucial for disease prevention, underlining the importance of well-planned vaccination strategies. Moreover, the numerical simulations validate all the theoretical findings, emphasizing the validity of this model in a real-world situation. Relying solely on vaccination might not swiftly or completely control the disease. Complementary pharmaceutical and non-pharmaceutical measures are necessary to combat the infection effectively. Further limitations on medical resources could lead to a backward bifurcation. Simulation results suggest that delaying the implementation of control measures could exacerbate epidemic situations.
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    Impact of chemo-immunotherapy on tumour-immune interactions: a non-autonomous model of tumor necrosis factor and T cell dynamics
    (2025) Dubey, Uma S.; Dubey, Balram
    This study explores the interaction between cancer cells, helper T cells, cytotoxic T cells, and tumour necrosis factors in chemotherapy and immunotherapy treatment in the microenvironment [1]. The goal is to analyze the connection of helper and cytotoxic T-cell levels with the anti-tumour immune response and the impact of various dosing regimens when combined with immunotherapy and chemotherapy. These protocols aim to shorten the interval between treatment cycles from three to two weeks or less to prevent tumour regrowth and maximize its cell elimination by treatment. Motivated by clinical trials, we thoroughly compare procedures involving two medications supplied sequentially or simultaneously in a non-autonomous system. We discussed the positivity and boundedness of the model. Further, we analyze the biologically valid equilibria and investigate their local stability properties, examining transcritical, saddle-node, Hopf, and Bogdanov-Takens bifurcations numerically and analytically [2]. Furthermore, direction and stability conditions for periodic solutions are determined.
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    Bifurcation and chaotic dynamics in a spatiotemporal epidemic model with delayed optimal control, stochastic process, and sensitivity analysis
    (AIP, 2025-03) Dubey, Uma S.; Dubey, Balram
    This study introduces an epidemic model with a Beddington–DeAngelis-type incidence rate and Holling type II treatment rate. The Bedding- ton–DeAngelis incidence rate is used to evaluate the effectiveness of inhibitory measures implemented by susceptible and infected individuals. Moreover, the choice of Holling type II treatment rate in our model aims to assess the impact of limited treatment facilities in the context of disease outbreaks. First, the well-posed nature of the model is analyzed, and then, we further investigated the local and global stability analysis along with bifurcation of co-dimensions 1 (transcritical, Hopf, saddle-node) and 2 (Bogdanov–Takens, generalized Hopf) for the system. Moreover, we incorporate a time-delayed model to investigate the effect of incubation delay on disease transmission. We provide a rigorous demonstration of the existence of chaos and establish the conditions that lead to chaotic dynamics and chaos control. Additionally, sensitivity analysis is performed using partial rank correlation coefficient and extended Fourier amplitude sensitivity test methods. Furthermore, we delve into optimal control strategies using Pontryagin’s maximum principle and assess the influence of delays in state and control parame- ters on model dynamics. Again, a stochastic epidemic model is formulated and analyzed using a continuous-time Markov chain model for infectious propagation. Analytical estimation of the likelihood of disease extinction and the occurrence of an epidemic is conducted using the branching process approximation. The spatial system presents a comprehensive stability analysis and yielding criteria for Turing instability. Moreover, we have generated the noise-induced pattern to assess the effect of white noise in the populations. Additionally, a case study has been conducted to estimate the model parameters, utilizing COVID-19 data from Poland and HIV/AIDS data from India. Finally, all theo- retical results are validated through numerical simulations. This article extensively explores various modeling techniques, like deterministic, stochastic, statistical, pattern formation(noise-induced), model fitting, and other modeling perspectives, highlighting the significance of the inhibitory effects exerted by susceptible and infected populations.
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    Camel Milk α-lactalbumin As A Potential Anticancer Molecule: A Bioinformatics Analysis
    (Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2020) Dubey, Uma S.
    α-lactalbumin-Oleic acid complex derived from milk is well known to have anti-cancer properties in many diverse mammalian species including humans, goats and cows. The objective of the current study is to see if α-lactalbumin present in camel’s milk too can serve as a potential anti-cancer molecule in its complex form. A comparative evaluation of α-lactalbumin structure among four mammalian species, viz, Camelusferus, Bostaurus, Homo sapiens, and Capra hircus has been made between the nucleotide sequences and structures of protein. Furthermore, the physico-chemical properties, amino acid composition, position of disulfide bridge formation in these species has been compared. The outcome of the present study suggests the presence of an anti-cancer property in the α-lactalbumin of camel, as has been experimentally observed in the other three species.